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- Chronic thromboembolic pulmonary hypertension: initial experience of patients undergoing pulmonary thromboendarterectomyPublication . Plácido, Rui; Guimarães, Tatiana; Jenkins, David; Cortez-Dias, Nuno; Couto Pereira, Sara Cristina; Campos, Paula; Mineiro, Ana; Lousada, Nuno; Martins, Susana; Moreira, Susana; Dias, Ana Rocha; Resende, Catarina; Vieira, Rita; Pinto, Fausto J.Introduction and objectives: Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center. Methods: Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA. Results: 27 consecutive patients (59% female) with a median age of 60 (49-71) years underwent PEA. During a median follow-up of 34 (21-48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42-59) mmHg to 26 (22-38) mmHg, an increase in cardiac output from 3.3 (2.9-4.0) L/min to 4.9 (4.2-5.5) L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2-15.5) uW to 3.5 (2.6-5,2) uW. During the follow-up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n=3) had PH recurrence. There was a reduction of N-terminal pro-B-type natriureticpeptide from 868 (212-1730) pg/mL to 171 (98-382) pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13-14) mm and 9 (8-10) cm/s to 17 (16-18) mm and 13 (11-15) cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six-minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test. Conclusion: Pulmonary endarterectomy performed at an experienced high-volume center is a safe procedure with a very favorable medium-term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.
- Changes in expression of the CLOCK gene in obstructive sleep apnea syndrome patients are not reverted by continuous positive airway pressure treatmentPublication . Moreira, Susana; Rodrigues, Raquel; Barros, André; Pejanovic, Nada; Neves-Costa, Ana; Pedroso, Dora; Pereira, Cláudia; Fernandes, Dina; Rodrigues, João Valença; Bárbara, Cristina; Moita, LuisPurpose: Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment. Methods: Peripheral blood was collected from male patients diagnosed with severe OSAS (apnea-hypopnea index ≥ 30/h) before and after treatment initiation. qPCR was used to measure mRNA levels of genes associated with the central circadian pacemaker including CLOCK, BMAL1, Cry1, Cry2, and three Period genes (Per 1, 2, 3) in peripheral blood mononuclear cells (PBMCs). Results: We found statistically significant differences for CLOCK (p-value = 0.022) expression in PBMCs of OSAS patients which were not reverted by treatment with CPAP. We have also found a substantial decrease in the slow wave sleep (SWS) content in OSAS patients (p-value < 0.001) that, contrary to REM sleep, was not corrected by CPAP (p-value = 0.875). Conclusion: CPAP treatment does not correct substantial changes in expression of core clock genes in OSAS patients. Because CPAP treatment is also unable to normalize the SWS in these patients, it is likely that additional therapeutic interventions that increase SWS content and complement the benefits of CPAP are required to more effectively reduce the known increased cardiovascular risk associated with OSAS patients.
- A protocol to evaluate retinal vascular response using optical coherence tomography angiographyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Aguiar, Patrício; Dionísio, Patrícia; Pinto, Luis; Castanho, Miguel A. R. B.; Marques-Neves, CarlosIntroduction: Optical coherence tomography angiography (OCT-A) is a novel diagnostic tool with increasing applications in ophthalmology clinics that provides non-invasive high-resolution imaging of the retinal microvasculature. Our aim is to report in detail an experimental protocol for analyzing both vasodilatory and vasoconstriction retinal vascular responses with the available OCT-A technology. Methods: A commercial OCT-A device was used (AngioVue®, Optovue, CA, United States), and all examinations were performed by an experienced technician using the standard protocol for macular examination. Two standardized tests were applied: (i) the hypoxia challenge test (HCT) and (ii) the handgrip test, in order to induce a vasodilatory and vasoconstriction response, respectively. OCT-A was performed at baseline conditions and during the stress test. Macular parafoveal vessel density of the superficial and deep plexuses was assessed from the en face angiograms. Statistical analysis was performed using STATA v14.1 and p < 0.05 was considered for statistical significance. Results: Twenty-four eyes of 24 healthy subjects (10 male) were studied. Mean age was 31.8 ± 8.2 years (range, 18–57 years). Mean parafoveal vessel density in the superficial plexus increased from 54.7 ± 2.6 in baseline conditions to 56.0 ± 2.0 in hypoxia (p < 0.01). Mean parafoveal vessel density in the deep plexuses also increased, from 60.4 ± 2.2 at baseline to 61.5 ± 2.1 during hypoxia (p < 0.01). The OCT-A during the handgrip test revealed a decrease in vessel density in both superficial (55.5 ± 2.6 to 53.7 ± 2.9, p < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, p < 0.001) parafoveal plexuses. Discussion: In this work, we detail a simple, non-invasive, safe, and non-costly protocol to assess a central nervous system vascular response (i.e., the retinal circulation) using OCT-A technology. A vasodilatory response and a vasoconstriction response were observed in two physiologic conditions—mild hypoxia and isometric exercise, respectively. This protocol constitutes a new way of studying retinal vascular changes that may be applied in health and disease of multiple medical fields.
- Chronic thromboembolic pulmonary hypertension: a comprehensive review of pathogenesis, diagnosis, and treatment strategiesPublication . Cazeiro, Daniel; Azaredo Raposo, Miguel; Guimarães, Tatiana; Lousada, Nuno; Jenkins, David; Inácio, João R.; Moreira, Susana; Mineiro, Ana; Freitas, Céline; Martins, Susana; Ferreira, Ricardo; Luís, Rita; Cardim, Nuno; Pinto, Fausto J.; Plácido, RuiChronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.
- Retinal vascular reactivity in type 1 diabetes patients without retinopathy using optical coherence tomography angiographyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Aguiar, Patrício; Dionísio, Patrícia; Pinto, Luis; Castanho, Miguel A. R. B.; Marques-Neves, CarlosPurpose: We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. Methods: Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. Results: In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F1,23 = 15.69, P < 0.001 and F1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F1,23 = 27.37, P < 0.0001 and F1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F1,23 = 11.04, P < 0.01). Conclusions: Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.
- Complex sleep-disordered breathing after vagus nerve stimulation: broadening the spectrum of adverse events of special interestPublication . Oliveira Santos, Miguel; Bentes, Carla; Teodoro, Tiago; Moreira, Susana; Marques, Marta; Tomé, Diogo; Peralta, AnaTwo young males with refractory epilepsy of unknown aetiology were referred for vagus nerve stimulation (VNS). Sleep disturbances emerged following VNS parameter changes. In Patient 1, video-polysomnogram (PSG) disclosed snoring and catathrenia in non-REM sleep. Central apnoea also occurred, but more rarely. In Patient 2, video-PSG showed mixed apnoea with desaturation and episodes of stridor followed by a catathrenia-like sound. A drug-induced sleep endoscopy (DISE) revealed, during VNS OFF time, glossoptosis, "trap door" of the epiglottis, and paresis of the left side of the larynx and ipsilateral vocal cords. During ON time, there were periods of pharyngeal collapse, in which video-PSG revealed patterns suggestive of both obstructive and central sleep apnoea. All these sleep-related phenomena were coincident with VNS ON time. In the first patient, VNS parameter adjustment was sufficient to successfully reverse all the symptoms, whereas the other patient required concomitant treatment with continuous positive airway pressure. The data broaden our knowledge about sleep disorders related to VNS, in particular stridor and catathrenia. We suggest that central sleep apnoea may be associated with laryngeal occlusion. DISE may be considered in selected cases as a valuable clinical tool to evaluate, in a single session, the effectiveness of multiple VNS parameter changes on respiration and laryngeal side effects.
- Optical coherence tomography angiography study of the retinal vascular plexuses in type 1 diabetes without retinopathyPublication . Sousa, David Cordeiro; Leal, Ines; Moreira, Susana; Vale, Sónia do; Silva-Herdade, Ana S.; Dionísio, Patrícia; Castanho, Miguel A. R. B.; Pinto, Luis; Marques-Neves, CarlosAim Previous data suggest the existence of retinal vascular changes and impaired autoregulation in the very early stages of diabetic retinopathy (DR). We compared the retinal plexuses between patients with type 1 diabetes (T1D) without DR and a demographically similar healthy cohort, using optical coherence tomography angiography (OCT-A). Methods Patients with T1D and no signs of DR were prospectively recruited from an outpatient clinic. Using OCT-A (AngioVue®), the parafoveal superficial (SCP) and deep (DPC) capillary plexus as well as the foveal avascular zone (FAZ) and perimeter were gathered. Mean comparison tests and linear regression analysis were used as statistical tests (STATA v14). Results Studied population included 48 subjects (24 T1D). The analysis of SCP revealed an attenuation of the capillary network compared with the control group in both parafoveal (51.8 ± 4.5 vs. 55.8 ± 3.2, p < 0.001) and perifoveal (51.9 ± 3.3 vs. 53.9 ± 1.9, p = 0.01) regions. A similar finding was observed in the DCP for both parafoveal (56.4 ± 4.3 vs. 60.4 ± 2.2, p < 0.001) and perifoveal (54.7 ± 3.9 vs. 60.8 ± 3.4, p = 0.001) sectors. Also, a longer time since T1D diagnosis was associated with a larger FAZ area (p = 0.055) and perimeter (p = 0.03). Conclusions Significant differences in the retinal microvasculature were observed between healthy subjects and T1D patients using OCT-A, even before clinically detectable disease on fundus biomicroscopy.